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Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 [R. C. J., G. W.], and the Department of Biochemistry, Howard University Medical College, Washington, D. C. 20001 [H. P. M.]
The three enzymes of the purine ribonucleotide cycle, adenylosuccinate synthetase, adenylosuccinase, and adenylate deaminase, were studied in rat liver, in a series of transplantable hepatomas of different growth rates, and in rat kidney cortex and transplantable kidney tumors. The activities of the three enzymes were significantly increased in all the tumors; adenylate deaminase also correlated with hepatoma growth rate. The three enzyme activities did not change in regenerating liver. In the average liver cell of neonatal rats, adenylosuccinate synthetase, adenylosuccinase, and adenylate deaminase activities were 8, 18, and 67%, respectively, of the adult level. The properties of adenylosuccinate synthetase and adenylosuccinase were similar in normal liver and in rapidly growing hepatoma 3924A. Adenylate deaminase in hepatoma 3924A, however, differed markedly from the normal liver enzyme; whereas the liver enzyme eluted from diethylaminoethyl-Sephadex A-50 as a single peak, the hepatoma 3924A deaminase eluted in three peaks. The first of these was a very minor component; the second, which accounted for two-thirds of the total activity, had the chromatographic and kinetic properties of the rat muscle enzyme; and the third component resembled normal rat liver adenylate deaminase.
The marked increase in activities of the purine cycle enzymes indicates an increased capacity of the transformed liver cell for the biosynthesis of adenine nucleotides and for their reconversion to inosine 5'-monophosphate, which is also a precursor of guanine nucleotides.
1 Recipient of USPHS Grant CA-18129. To whom requests for reprints should be addressed, at the Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis, Ind. 46202.
2 Recipient of USPHS Grant CA-10792.
3 Recipient of USPHS Grants CA-13526 and CA-05034.
Received 3/21/77. Accepted 6/ 2/77.
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